fr901228 in treating patients with previously treated unresectable locally advanced or metastatic colorectal cancer

Conditions: Colorectal Cancer

Summary: rationale: drugs used in chemotherapy, such as fr901228, work in different ways to stop tumor cells from dividing so they stop growing or die. purpose: this phase ii trial is studying how well fr901228 works in treating patients with unresectable locally advanced or metastatic colorectal cancer.

objectives: * determine the confirmed response (complete and partial) in patients with previously treated unresectable locally advanced or metastatic colorectal cancer treated with fr901228 (depsipeptide). * determine the time to treatment failure and overall survival of patients treated with this drug. * determine the qualitative and quantitative toxic effects of this drug in these patients. outline: this is a multicenter study. patients receive fr901228 (depsipeptide) iv over 4 hours on days 1, 8, and 15. courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. patients are followed every 8 weeks until disease progression and then every 3 months until 1 year after study entry and then every 6 months until 3 years after study entry. projected accrual: a total of 20-40 patients will be accrued for this study within 4-10 months.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed colorectal cancer meeting 1 of the following criteria: * locally advanced unresectable disease * distant metastatic disease * measurable disease * previously treated with at least 1, but no more than 2, prior chemotherapy regimens for unresectable locally advanced or metastatic disease * may have included irinotecan or oxaliplatin * no more than 1 prior chemotherapy regimen (not oxaliplatin-based) for advanced or metastatic disease if previously treated with oxaliplatin-based adjuvant chemotherapy * no more than 1 prior chemotherapy regimen (not irinotecan-based) for advanced or metastatic disease if previously treated with irinotecan-based adjuvant chemotherapy * no known brain metastases patient characteristics: age * over 18 performance status * zubrod 0-1 life expectancy * not specified hematopoietic * wbc ≥ 3,000/mm\^3 * absolute neutrophil count ≥ 1,500/mm\^3 * platelet count ≥ 100,000/mm\^3 hepatic * bilirubin ≤ upper limit of normal (uln) * sgot and sgpt ≤ 2.5 times uln renal * creatinine ≤ uln cardiovascular * no new york heart association class iii or iv congestive heart failure * no myocardial infarction within the past year * no uncontrolled dysrhythmias * no poorly controlled angina * no prior serious ventricular arrhythmia (e.g., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row) * no left ventricular hypertrophy * qtc \< 500 msec * no other significant cardiac disease other * not pregnant or nursing * fertile patients must use effective contraception * no other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * no prior allergic reaction attributed to compounds of similar chemical or biological composition to fr901228 prior concurrent therapy: biologic therapy * no concurrent anticancer immunotherapy chemotherapy * see disease characteristics * at least 28 days since prior chemotherapy and recovered * no prior fr901228 (depsipeptide) * no other concurrent anticancer chemotherapy endocrine therapy * no concurrent anticancer hormonal therapy radiotherapy * at least 28 days since prior radiotherapy and recovered * no concurrent anticancer radiotherapy surgery * at least 28 days since prior surgery and recovered other * no concurrent combination antiretroviral therapy for hiv-positive patients * no concurrent agent that causes qtc prolongation * no concurrent hydrochlorothiazide * no other concurrent investigational agents * no other concurrent drugs that have histone deacetylase inhibitor activity (e.g., valproic acid) * no other concurrent anticancer therapy

Keywords: recurrent colon cancer stage iii colon cancer stage iv colon cancer recurrent rectal cancer stage iii rectal cancer stage iv rectal cancer